Praseodymium-induced pinacol formation

Article abstract of DOI:10.1080/00397910802369646

In an attempt to regenerate Ti(0) from TiOx for possible application in a catalytic McMurry coupling reaction, a praseodymium-based pinacol reaction was uncovered. This reaction formed the two products 2,3-diphenyl-2,3-butanediol (3) and α,β-dimethyl-α-phenyl-β-[(trimethylsilyl)oxy]- benzene-ethanol (6) in a 1:3 ratio. Copyright Taylor & Francis Group, LLC.

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Praseodymium-Induced Pinacol
Formation
Jeanette R. Drapo a & Ronny Priefer a
a Department of Chemistry and Biochemistry ,
Niagara University, Niagara University , New York,
USA
Published online: 15 Feb 2011.
To cite this article: Jeanette R. Drapo & Ronny Priefer (2008) Praseodymium-
Induced Pinacol Formation, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:1, 85-92, DOI:
10.1080/00397910802369646
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Synthetic Communications1, 39: 85–92, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802369646
Praseodymium-Induced Pinacol Formation
Jeanette R. Drapo and Ronny Priefer
Department of Chemistry and Biochemistry, Niagara University,
Niagara University, New York, USA
Abstract: In an attempt to regenerate Ti(0) from TiOx for possible application in
a catalytic McMurry coupling reaction, a praseodymium-based pinacol reaction
was uncovered. This reaction formed the two products 2,3-diphenyl-2,3-
butanediol (3) and a,b-dimethyl-a-phenyl-b-[(trimethylsilyl)oxy]-benzene-ethanol
(6) in a 1:3 ratio.
Keywords: Cross-coupling, pinacol, praseodymium
INTRODUCTION
The McMurry reaction has been shown to be a very versatile methodology,
allowing for the coupling of ketones, aldehydes, and some esters and
amide.[1–8] The key to this coupling is the formation in situ of Ti(0) from
TiClx using a reducing agent, typically zinc or LiAlH4.[9] Because of the
expense and hazards associated with TiCl4, a route using a catalytic
amount of the Ti source would be ideal. In 1995 Furstner and Hupperts
¨
reported that the reaction could be performed using only catalytic
amounts of low-valent titanium in the presence of a chlorosilane.[10]
The key to their reaction was the in situ regeneration of titanium chloride
from the titanium oxides by the chlorosilane.[10] This reaction required
stoichiometric amounts of both chlorotrimethylsilane (TMSCl) and Zn.
It was our initial hope to regenerate not TiCl4, but Ti(0) directly.
Received May 23, 2008.
Address correspondence to Ronny Priefer, Department of Chemistry and Bio-
chemistry, Niagara University, Niagara University, NY 14109, USA. E-mail:
rpriefer@niagara.edu
85

86
J. R. Drapo and R. Priefer
As this method focused on the regeneration of Ti(0) from TiOx we
examined metals that could reduce the titanium oxides. In theory, a metal
with a higher M ¼ O bond energy than TiOx, or a favorable electrochemi-
cal potential, should regenerate Ti(0). This could induce the reaction to go
catalytically with respect to titanium. Our approach was to systematically
evaluateappropriatemetals(i.e.,boron,carbon,silicon,beryllium,german-
ium, aluminum, niobium, and praseodymium) that we hoped could react
in situ with catalytic amounts of either TiO or TiO2 to produce Ti(0), such
that the reaction would proceed catalytically with respect to titanium.
RESULTS AND DISCUSSION
Initially, we examined the effect of catalytic amounts of TiCl4 on a
McMurry coupling reaction using acetophenone (1). Under classic
McMurry conditions (1:3:6) of ketone–TiCl4–Zn, a 100% conversion to
the 2,3-diphenyl-but-2-ene (2) product was observed by 1HNMR. By alter-
ing the ratio of TiCl4 and Zn, predominantly non-McMurry products were
formed (Scheme 1, Table 1). The reactions of acetophenone with 0.2 and 0.1
equivalents of TiCl4 yielded 2,3-diphenyl-2,3-butanediol (3) as the main pro-
duct, with 35 and 70% starting material remaining, respectively. However,
when only 0.05 equivalents of TiCl4 were used, 2-butanone-3,3-diphenyl
(4) was the major product. It is thought that the lower equivalence of TiCl4
favors the formation of the pinacol product; however, at the lowest equiva-
lence, the rearrangement yielding 4 occurred. Although not noted in Table 1,
there was a very small amount (<0.1%) of 1-propanone-2-methyl-1,2-diphe-
nyl (5) also present when 0.05 equivalents of TiCl4 were used.
We next examined the use of elemental metals on the classic
McMurry coupling reaction. The reaction was initiated by mixing of
TiCl4 and Zn, and subsequently a metal, and then acetophenone were
added. Table 2 shows the results of reacting catalytic amounts of TiCl4
Scheme 1. Products formed using different amounts of TiCl4.

Praseodymium-Induced Pinacol Formation
87
Table 1. Reaction using varying amounts of TiCl4 (classic McMurry coupling
reaction was included as a point of reference)
Non-
McMurry McMurry Starting Non-McMurry
Aceto-
phenone TiX
product producta materiala
product(s)
produced
Zn Metal (2)a (%)
(%)
(%)
1 eq
1 eq
1 eq
1 eq
TiCl4 6 eq
3 eq
TiCl4 0.4 eq
0.2 eq
TiCl4 0.2 eq
0.1 eq
TiCl4 0.1 eq
0.05 eq
—
—
—
—
100
0.5
0
0
—
63.9
29.3
13.9
35.6 2,3-Diphenyl-2,
3-butanediol (3)
70.5 2,3-Diphenyl-2,
3-butanediol (3)
85.9 2-Butanone-3,
3-diphenyl (4)
0.2
0.2
1
aNonisolated yields, percentage via HNMR.
Table 2. Reacting catalytic amounts of TiCl4 in the presence of an additional
metal (classic McMurry coupling reaction was used as a point of reference)
Non-
McMurry McMurry Starting Non-McMurry
Aceto-
phenone TiX Zn Metal (2)a (%)
product producta materiala
product(s)
produced
(%)
(%)
1 eq
1 eq
1 eq
1 eq
1 eq
1 eq
1 eq
1 eq
1 eq
TiCl4 6 eq
3 eq
TiCl4 0.2 eq B 2 eq
0.1 eq
TiCl4 0.2 eq C 2 eq
0.1 eq
TiCl4 0.2 eq Si 2 eq
0.1 eq
TiCl4 0.2 eq Be 2 eq
0.1 eq
TiCl4 0.2 eq Ge 2 eq
0.1 eq
TiCl4 0.2 eq Al 2 eq
0.1 eq
TiCl4 0.2 eq Nb 2eq
0.1 eq
—
100
1.8
0
0
—
32.6
26.1
34.7
0
65.6 2-Butanone-3,
3-diphenyl (4)
67.2 2-Butanone-3,
3-diphenyl (4)
64.2 2-Butanone-3,
3-diphenyl (4)
100
6.7
1.1
0
—
—
—
—
—
0
0
100
100
100
100
0
0
0
0
TiCl4 0.2 eq Pr 2 eq
0.1 eq
0
0
1
aNonisolated yields, percentage via HNMR.

88
J. R. Drapo and R. Priefer
and acetophenone in the presence of the various metals. In the three cases
where a reaction occurred, compound 4 was predominantly observed
with only small amounts of the desired McMurry product. Addition of
boron, carbon, and silicon gave similar results; however, the reaction
was completely suppressed when using beryllium, germanium, aluminum,
niobium, and praseodymium. This suggests that although the addition of
boron, carbon, and silicon does not facilitate a catalytic McMurry coup-
ling, it does increase the pinacol rearrangement to 2-butanone-3,
3-diphenyl (4). In addition, beryllium, germanium, aluminum, niobium,
and praseodymium completely quenched the reaction.
In a hope to reduce other titanium source to their active form, Ti,
TiO, and TiO2 were initially individually mixed with various metals
before acetophenone was added. Attempts were made with boron,
carbon, silicon, beryllium, germanium, aluminum, niobium, and praseo-
dymium. Unfortunately none of the reactions gave any product, and only
starting acetophenone was recovered.
These unsuccessful results suggested that it may be necessary to use a
Furstner approach of converting the TiO back to TiCl initially with the
¨
x
4
use of alternate metals to possibly reduce the TiCl4 to Ti(0). Initially we
performed the reaction using TiCl4 as opposed to TiCl3, as reported.[10]
The reaction was successful, and not surprisingly when Ti, TiO, TiO2
were used as the titanium source the reaction was unsuccessful, suggest-
ing that TMSCl alone in the presence of various sources of titanium is not
responsible for the formation of any product.
We then examined the use of various sources of titanium and acetophe-
none in the presence of carbon or praseodymium and TMSCl (Table 3). All
of the reactions using carbon as the additional metal source failed; however,
praseodymium yielded two products, 2,3-diphenyl-2,3-butanediol (3)
and a,b-dimethyl-a-phenyl-b-[(trimethylsilyl)oxy]-benzene-ethanol (6) in a
1:3 ratio (Scheme 2). As indicated earlier, there were no reactions observed
when Pr was used alone, and because the reaction was unsuccessful with all
the titanium sources (except TiCl4) when TMSCl was used alone we
removed the titanium from the reaction to see if this pinacol formation
was praseodymium induced. This reaction did indeed afford our two pro-
ducts, 3 and 6, in comparable yields and ratios. Hirao et al. had reported
a similar pinacol formation with rare-earth metals, such as praseodymium;
however, they did not obtain any mono-TMS protected product.[11]
EXPERIMENTAL
All reactions were performed under an argon atmosphere with anhydrous
THF. All commercial reagents were obtained from Sigma-Aldrich

89

90
J. R. Drapo and R. Priefer
Scheme 2. Pinacol reaction using praseodymium and TMSCl.
Chemical Company. Thin-layer chromatography (TLC) was performed
on 0.25-mm silica-gel plates with aluminum backing, visualized using
short-wave UV light. Column chromatography was carried out on silica
gel (230–400 mesh) using flash-chromatography conditions.
1H and 13CNMR were recorded on a Varian 400-MHz instrument,
and all synthesized compounds were compared to previously reported
spectra.
Classic McMurry Coupling Reaction
In a round-bottom flask with an attached condenser, anhydrous THF
was added to zinc (6 eq) under argon. The suspension was cooled down
to 0 ꢀC. TiCl4 (3 eq) was slowly added to the round-bottom flask via the
top of the condenser. The mixture was then refluxed for 45 min, thus
reducing the TiCl4 to Ti(0). The reaction flask was then brought down
to room temperature, and acetophenone (1 eq) was added. The reaction
was refluxed for 24 h. After cooling to room temperature, the mixture
was quenched with water, extracted with EtOAc, washed with water,
dried with MgSO4, filtered, and the solvent was removed using a rotary
evaporator. The off-white solid was purified via column chromatography
1
(4:1 hexanes–EtOAc), and the structure was verified with HNMR to be
trans-2,3-diphenyl-2-butene, 2.
Fu¨rstner Procedure
To a zinc (1 eq)=THF suspension at 0 ꢀC, TiCl4 (0.11 eq) was slowly
added. The mixture was then refluxed for 45 min followed by cooling
to room temperature, and TMSCl (1 eq) and acetophenone (1 eq) were
added. The reaction was refluxed for 24 h, cooled to room temperature,
quenched with water, extracted with EtOAc, washed with water, dried
with MgSO4, and filtered, and the solvent was removed using a rotary
evaporator. The off-white solid was purified via column chromatography
1
(4:1 hexanes–EtOAc), and the structure was verified with HNMR to be
trans-2,3-diphenyl-2-butene, 2.

Praseodymium-Induced Pinacol Formation
91
Modification of Classic McMurry Coupling Reaction
This reaction took place as reported previously with the exception of
altered TiCl4 and Zn quantities, and=or addition of metals 5 min before
acetophenone, or replacement of TiCl4 and Zn with Ti, TiO, or TiO2.
Modification of Furstner Procedure
This reaction took place as reported previously with the exception of
replacement of TiCl4 and Zn with Ti, TiO, or TiO2, and=or altered
TMSCl quantities, and=or addition of metals 5 min before acetophenone.
CONCLUSION
Our main objective, to obtain a catalytic McMurry coupling reaction,
was unsuccessful; however, a novel approach to performing a pinacol
reaction was observed. Praseodymium has surfaced as a metal of interest
for pinacol reactions. Work on using alternate chlorosilanes, as well as
different carbonyl sources, is currently being examined.
ACKNOWLEDGMENTS
The authors thank Niagara University Academic Center for Integrated
Science and the Rochester Academy of Science for their financial support.
REFERENCES
1. Sawada, T.; Morita, M.; Chifuku, K.; Kuwahara, Y.; Shosenji, H.; Takafuji,
M.; Ihara, H. [1.1]meta-Stilbenophanes as calixarene analogs: Preparation,
crystal structure, and cis-trans photoisomerization. Tetrahedron Lett. 2007,
48(51), 9051–9055.
2. Duan, X.-F.; Zeng, J.; Zhang, Z.-B.; Zi, G.-F. A facile two-step synthesis of
2-arylbenzofurans based on the selective cross McMurry couplings. J. Org.
Chem. 2007, 72(26), 10283–10286.
3. Ikeda, H.; Sakai, Azusa: Namai, H.; Kawabe, A.; Mizuno, K. Synthesis,
x-ray crystallographic analysis, and theoretical structure analysis of tetrathie-
nylethenes designed for photo- and electrochromism. Tetrahedron Lett. 2007,
48(47), 8338–8342.
4. Shimasaki, T.; Kato, S.-I.; Shinmyozu, T. Synthesis, structural, spectral, and
photoswitchable properties of cis- and trans-2,2,20,20-tetramethyl-1,10-indany-
lindanes. J. Org. Chem. 2007, 72(16), 6251–6254.

92
J. R. Drapo and R. Priefer
5. Jeong, H. J.; Yoon, U. Y.; Jang, S. H.; Yoo, U.-A.; Kim, S. N.; Truong, B. T.;
Shin, S. C.; Yoon, Y.-J.; Singh, O. M.; Lee, S.-G. A new Zn=TiCl4=LiAlH4
mediated approach to 2-aryl- or 2-alkyl-substituted benzothiophenes via
intramolecular cyclization. Synlett 2007, 9, 1407–1410.
6. Juhasz, L.; Szilagyi, L.; Antus, S.; Visy, J.; Zsila, F.; Simonyi, M. New insight
into the mechanism of hypervalent iodine oxidation of flavanones. Tetra-
hedron 2002, 58(21), 4261–4265.
7. Furstner, A.; Hupperts, A.; Ptock, A.; Janssen, E. ‘‘Site selective’’ formation
¨
of low-valent titanium reagents: An ‘‘instant’’ procedure for the reductive
coupling of oxo amides to indoles. J. Org. Chem. 1994, 59(18), 5215–5229.
8. Jones, C. P.; Anderson, K. W.; Buchwald, S. L. Sequential Cu-catalyzed
amidation-base-mediated Camps cyclization: A two-step synthesis of 2-aryl-
4-quinolones from o-halophenones. J. Org. Chem. 2007, 72(21), 7968–7973.
9. McMurry, J. E.; Fleming, M. P. New method for the reductive coupling of
carbonyls to olefins. Synthesis of b-carotene. J. Am. Chem. Soc. 1974, 96(14),
4708–4709.
10. Furstner, A.; Hupperts, A. Carbonyl coupling reactions catalytic in titanium
¨
and the use of commercial titanium powder for organic synthesis. J. Am.
Chem. Soc. 1995, 117(16), 4468–4475.
11. Ogawa, A.; Takeuchi, H.; Hirao, T. Diastereoselective pinacol coupling of
alkyl aryl ketones with rare earth metals in the presence of chlorosilanes.
Tetrahedron Lett. 1999, 40(39), 7113–7114.